PROJECT SUMMARY/ABSTRACT Epigenetics refers to heritable changes in gene expression and/or phenotype without mutations in DNA sequences. Histone modifications including methylation, acetylation and phosphorylation as well as modifications on DNA such as DNA methylation and hydroxymethylation are epigenetic marks. These epigenetic marks are critical to regulate gene expression. Changes in histone modifications have also been observed in the Epidemiology of Diabetic Interventions and Complications (EDIC) study and is proposed to confer ?memory? of hyperglycemia. However, it is largely unexplored on how epigenetic alterations contribute to the development of diabetic gastroparesis. In this program project grants, all three projects will analyze epigenetic changes during diabetic development using mouse models and human patient samples using epigenomic methods including ChIP-seq. ChIP-seq and MeDIP-seq are state of art techniques to analyze histone modifications and DNA methylation, respectively, on a genome-wide scale. While these approaches may be considered standard practice for highly focused epigenomic laboratories, they are not for most laboratories and institutions including the 3 Project laboratories. The Epigenomic and Transcriptomic Core (Core B) will have designated scientists to provide expertise supporting each program project, will establish a set of common protocols and procedures for acquisition of reliable and comparable epigenomic and transcriptomic data, and provide tertiary bioinformatics support to analyze the epigenome and transcriptome to gain insight into the impact of epigenetic changes on diabetic gastroparesis. The work of this Core will support the needs of each Project, help obtain reliable datasets, facilitate the successful completion of each program project and reduce cost.